Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Agonists
- Antagonists
- Immunopharmacology Comments
- Immuno Process Associations
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 374 | 6q27 | CCR6 | C-C motif chemokine receptor 6 | 4,15,24 |
| Mouse | 7 | 367 | 17 A1 | Ccr6 | C-C motif chemokine receptor 6 | 21 |
| Rat | 7 | 366 | 1q12 | Ccr6 | C-C motif chemokine receptor 6 | |
| Previous and Unofficial Names |
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| CKR-L3 [24] | DCCR2 [19] | GPR-CY4 [4] | STRL22 [15] | DRY-6 | GPR29 | CD196 | |
| Database Links |
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| Specialist databases | |
| GPCRdb | ccr6_human (Hs), ccr6_mouse (Mm), q5bk58_rat (Rn) |
| Other databases | |
| Alphafold | P51684 (Hs), O54689 (Mm), Q5BK58 (Rn) |
| ChEMBL Target | CHEMBL4423 (Hs) |
| Ensembl Gene | ENSG00000112486 (Hs), ENSMUSG00000040899 (Mm), ENSRNOG00000012964 (Rn) |
| Entrez Gene | 1235 (Hs), 12458 (Mm), 308163 (Rn) |
| Human Protein Atlas | ENSG00000112486 (Hs) |
| KEGG Gene | hsa:1235 (Hs), mmu:12458 (Mm), rno:308163 (Rn) |
| OMIM | 601835 (Hs) |
| Orphanet | ORPHA377602 (Hs) |
| Pharos | P51684 (Hs) |
| RefSeq Nucleotide | NM_004367 (Hs), NM_009835 (Mm), NM_001013145 (Rn) |
| RefSeq Protein | NP_004358 (Hs), NP_033965 (Mm), NP_001013163 (Rn) |
| UniProtKB | P51684 (Hs), O54689 (Mm), Q5BK58 (Rn) |
| Wikipedia | CCR6 (Hs) |
| Natural/Endogenous Ligands |
| beta-defensin 4A {Sp: Human} |
| CCL20 {Sp: Human} , CCL20 {Sp: Mouse} , CCL20 {Sp: Rat} |
| de |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta-defensin 4A (previously known as beta defensin 2) has been shown to be chemotactic for cells expressing CCR6 [23]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| CCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. CCR6 is expressed on a variety of immune cells including memory and regulatory T-cells [12,16], naïve and activated B cells [13], dendritic cells [22] and Th17 T-cells [3]. CCR6 is the main chemokine receptor of Th17 cells, which are implicated in many chronic inflammatory conditions. In addition, CCR6 and its only known ligand CCL20, are up-regulated in tissues of patients with chronic inflammatory conditions (e.g. psoriasis, arthritic conditions and inflammatory bowel disease) [5,10-11]. |
| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gi/Go family | Calcium channel |
| References: 2 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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References
1. Ai LS, Liao F. (2002) Mutating the four extracellular cysteines in the chemokine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling. Biochemistry, 41 (26): 8332-41. [PMID:12081481]
2. Al-Aoukaty A, Rolstad B, Giaid A, Maghazachi AA. (1998) MIP-3alpha, MIP-3beta and fractalkine induce the locomotion and the mobilization of intracellular calcium, and activate the heterotrimeric G proteins in human natural killer cells. Immunology, 95 (4): 618-24. [PMID:9893054]
3. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Filì L, Ferri S, Frosali F et al.. (2007) Phenotypic and functional features of human Th17 cells. J Exp Med, 204 (8): 1849-61. [PMID:17635957]
4. Baba M, Imai T, Nishimura M, Kakizaki M, Takagi S, Hieshima K, Nomiyama H, Yoshie O. (1997) Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC. J Biol Chem, 272 (23): 14893-8. [PMID:9169459]
5. Celis R, Planell N, Fernández-Sueiro JL, Sanmartí R, Ramírez J, González-Álvaro I, Pablos JL, Cañete JD. (2012) Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features. Arthritis Res Ther, 14 (2): R93. [PMID:22541888]
6. Charbonnier AS, Kohrgruber N, Kriehuber E, Stingl G, Rot A, Maurer D. (1999) Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells. J Exp Med, 190 (12): 1755-68. [PMID:10601351]
7. Corcione A, Tortolina G, Bonecchi R, Battilana N, Taborelli G, Malavasi F, Sozzani S, Ottonello L, Dallegri F, Pistoia V. (2002) Chemotaxis of human tonsil B lymphocytes to CC chemokine receptor (CCR) 1, CCR2 and CCR4 ligands is restricted to non-germinal center cells. Int Immunol, 14: 883-892. [PMID:12147625]
8. Flynn G, Maru S, Loughlin J, Romero IA, Male D. (2003) Regulation of chemokine receptor expression in human microglia and astrocytes. J Neuroimmunol, 136 (1-2): 84-93. [PMID:12620646]
9. Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B, Franz-Bacon K, Rossi D, Caux C, McClanahan T, Gordon S et al.. (1997) CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells. J Exp Med, 186 (6): 837-44. [PMID:9294138]
10. Homey B, Dieu-Nosjean MC, Wiesenborn A, Massacrier C, Pin JJ, Oldham E, Catron D, Buchanan ME, Müller A, deWaal Malefyt R et al.. (2000) Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. J Immunol, 164 (12): 6621-32. [PMID:10843722]
11. Kaser A, Ludwiczek O, Holzmann S, Moschen AR, Weiss G, Enrich B, Graziadei I, Dunzendorfer S, Wiedermann CJ, Mürzl E et al.. (2004) Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol, 24 (1): 74-85. [PMID:14997037]
12. Kleinewietfeld M, Puentes F, Borsellino G, Battistini L, Rötzschke O, Falk K. (2005) CCR6 expression defines regulatory effector/memory-like cells within the CD25(+)CD4+ T-cell subset. Blood, 105 (7): 2877-86. [PMID:15613550]
13. Krzysiek R, Lefevre EA, Bernard J, Foussat A, Galanaud P, Louache F, Richard Y. (2000) Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells. Blood, 96 (7): 2338-45. [PMID:11001880]
14. Li W, Crouse KK, Alley J, Frisbie RK, Fish SC, Andreyeva TA, Reed LA, Thorn M, DiMaggio G, Donovan CB et al.. (2023) A Novel C-C Chemoattractant Cytokine (Chemokine) Receptor 6 (CCR6) Antagonist (PF-07054894) Distinguishes between Homologous Chemokine Receptors, Increases Basal Circulating CCR6+ T Cells, and Ameliorates Interleukin-23-Induced Skin Inflammation. J Pharmacol Exp Ther, 386 (1): 80-92. [PMID:37142443]
15. Liao F, Lee HH, Farber JM. (1997) Cloning of STRL22, a new human gene encoding a G-protein-coupled receptor related to chemokine receptors and located on chromosome 6q27. Genomics, 40 (1): 175-80. [PMID:9070937]
16. Liao F, Rabin RL, Smith CS, Sharma G, Nutman TB, Farber JM. (1999) CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha. J Immunol, 162 (1): 186-94. [PMID:9886385]
17. Lukacs NW, Prosser DM, Wiekowski M, Lira SA, Cook DN. (2001) Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation. J Exp Med, 194 (4): 551-5. [PMID:11514610]
18. Lügering A, Floer M, Westphal S, Maaser C, Spahn TW, Schmidt MA, Domschke W, Williams IR, Kucharzik T. (2005) Absence of CCR6 inhibits CD4+ regulatory T-cell development and M-cell formation inside Peyer's patches. Am J Pathol, 166 (6): 1647-54. [PMID:15920150]
19. Power CA, Church DJ, Meyer A, Alouani S, Proudfoot AE, Clark-Lewis I, Sozzani S, Mantovani A, Wells TN. (1997) Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells. J Exp Med, 186 (6): 825-35. [PMID:9294137]
20. Varona R, Villares R, Carramolino L, Goya I, Zaballos A, Gutiérrez J, Torres M, Martínez-A C, Márquez G. (2001) CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses. J Clin Invest, 107 (6): R37-45. [PMID:11254677]
21. Varona R, Zaballos A, Gutierrez J, Martín P, Roncal F, Albar JP, Ardavin C, Marquez G. (1998) Molecular cloning, functional characterization and mRNA expression analysis of the murine chemokine receptor CCR6 and its specific ligand MIP-3alpha. FEBS Lett, 440: 188-194. [PMID:9862452]
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23. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schröder JM, Wang JM, Howard OM et al.. (1999) Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science, 286 (5439): 525-8. [PMID:10521347]
24. Zaballos A, Varona R, Gutierrez J, Lind P, Marquez G. (1996) Molecular cloning and RNA expression of two new human chemokine receptor-like genes. Biochem Biophys Res Commun, 227: 846-853. [PMID:8886020]
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